Zachary, IC;
Mahmoud, M;
Evans, I;
Mehta, V;
Pellet-Many, C;
Paliashvili, K;
(2019)
Smooth muscle cell-specific knock out of Neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation.
American Journal of Physiology - Cell Physiology
, 316
(3)
C424-C433.
10.1152/ajpcell.00405.2018.
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Abstract
Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signalling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture, and is implicated in pathological SMC remodelling in vivo. To address the importance of Nrp1for SMC function during development, we generated conditional inducible Nrp1SMC-specific knockout mice. Induction of early postnatal SMC-specific Nrp1knockout led to pulmonary haemorrhage associated with defects in alveogenesis, and revealed a specific requirement for Nrp1in myofibroblast recruitment to the alveolar septae and PDGF-AA-induced migration in vitro. Furthermore, SMC-specific Nrp1knockout inhibited PDGF-BB-stimulated SMC outgrowth ex vivo in aortic ring assays, and reduced pathological arterial neointima formation in vivo. In contrast, we observed little significant effect of SMC-specific Nrp1knockout on neonatal retinal vascularisation. Our results point to a requirement of Nrp1in vascular smooth muscle and myofibroblast function in vivo, which may have relevance for post-natal lung development and for pathologies characterised by excessive SMC and/or myofibroblast proliferation.
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